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Journal PresentationImaging in gout: A review of the recent developments Keyko Septiyanti Widodo - 1102010143Fakultas Kedokteran Universitas Yarsi

AbstractGout is a common inflammatory arthritis and is caused by accumulation of monosodium urate crystals in joints and soft tissues Imaging tools can aid clinicians in establishing the correct diagnosis. Imaging can also be used to monitor treatment response. The imaging techniques that currently have a role in the imaging of gout include conventional radiography, ultrasound, computed tomography, dual energy computed tomography (DECT), magnetic resonance imaging and nuclear medicine.

Keywords: asymptomatic hyperuricemia, computed tomography, conventional radiography, dual energy computed tomography, erosions, magnetic resonance imaging, nuclear medicine, plane X-ray, tophus, ultrasound

IntroductionGout is common, indeed the most common inflammatory arthritis in men [Richette and Bardin, 2010]. Gout results from the deposition of monosodium urate (MSU) crystals in joints and soft tissues when serum uric acid concentrations rise above the physiological saturation limit (approximately 380 mol/liter or 6.4 mg/dl) [Choi et al. 2005]. The acute form of the arthritis is characterized by:Sudden onsetIntense painSwellingwarmtherythemaChronic tophus gout results from chronic hyperuricemia. Continued deposition of MSU crystals leads to:increased frequency of acute attacks, progressive shortening of intercriti- cal phase development of tophi due to MSU deposition in soft tissues, bones and joints.

The management of gout should be holistic, incorporating patient education, lifestyle advice, pharmacotherapy of acute gout, prophylaxis to prevent chronic tophus gout [Zhang et al. 2006a; Khanna et al. 2012].Imaging may play a useful role in this, particularly when uric acid crystals are unable to be identified to con- firm the diagnosis. Imaging can be useful to:assist with assessing disease burden and structural damage. monitor disease progression Monitor treatment response and to assess efficacy of treatment in clinical trials. Conventional Radiography (CR)CR has been the traditional imaging tool in the management of rheumatic disorders. During an acute attack of gout, soft tissue swelling and effusions may be seen by CR [Gentili, 2006], however these findings are nonspecific. The typical CR findings in chronic tophaceous gout, which differentiate it from other inflammatory arthritides, include well defined, punched-out erosions with overhanging edges, soft tissue nodules (tophi), calcification of tophi and asymmetric involvement [Gentili 2006] (Figure 1). CR may be a useful outcome tool in clinical trials as it is widely accessible and inexpensive, and while this is an old and simple imaging technique

Ultrasonography (US)US is being used increasingly in gout and can assist in both the diagnosis and monitoring of disease. Advantages of US over other imaging modalities include the ease of access, lack of ionizing radiation and relatively low cost. US however has limitations, being reliant upon a good acoustic window to visualize a joint, and is generally less sensitive than MRI in detecting joint inflammation and structural changes [Chowalloor and Keen, 2013b]. Recent exploratory studies in gout reports that synovitis is most commonly seen in the first MTP joint, knee, ankle, wrist and second metacarpophalangeal (MCP) joint [Chowalloor dan Keen, 2013a].

Generic signs of joint inflammation and damage identifiable by US include synovitis and erosions.Synovitis on US is identified as synovial hypertrophy and effusion [Wakefield et al. 2005].Erosions are cortical breaks seen in two planes (as defined by Outcome Measures in Rheumatology Clinical Trials, OMERACT) [Wakefield et al. 2005]. More specific features of gout are also seen, such as the double contour sign (DC) and tophi [Thiele dan Schlesinger, 2007; Filippucci et al. 2010a].In the setting of gout, the synovium may have an ultrasound appearance thought to be more suggestive of gout than other inflammatory arthritis. Reported descriptions include bright stippled foci and hyper-echoic spots, hyper-echoic cloudy areas and a snow storm appearance, which is thought to be a result of MSU crystals in synovial fluid or tissue producing small bright echoes [Wright et al. 2007; Rettenbacher et al. 2008; De Miguel et al. 2012](Figure 2)

The DC sign is a hyper-echoic irregular band over the articular cartilage due to the deposition of MSU crystals, best seen on the dorsal side of the MTP joints [Filippucci et al. 2010b] and femoral condyles [Naredo et al. 2013a] (Figure 4)

Other explanations include differences in methodology, joints examined, the demographics of the population, or that US is a user- dependent technique, and that the cartilage interface may produce an artefact that may be mistaken for a DC.

Tophus are typical clinical features of gout and have been variably described in US studies [Wright et al. 2007; Ottaviani et al. 2010; De vila Fernandes et al. 2011; Howard et al. 2011; Pineda et al. 2011; De Miguel et al. 2012]Various descriptions of tophi are referred to in the literature: (Figure 3)hypoechoic heterogeneous soft tissue deposit with or without post echoic shadowingiso-echoic/hyper-echoic nodular depositsbright spots and hyper-echoic areas [Chowalloor and Keen, 2013b]A recent study reported that common intra-articular sites for tophaceous deposits include the first MTP joint, radiocarpal joint, midcarpal joint and knees [Naredo et al. 2013a].The most common tendinous locations for tophi were the patellar and triceps tendon, followed by the quadriceps and Achilles tendons [Naredo et al. 2013a].

Computed Tomography (CT)CT is not commonly utilized in the clinical management of gout. Tophus appears on CT as hyperdense lesions, with their specific density allowing differentiation from other hyperdense lesions [Gerster et al. 1996]. CT can assess deep intra-articular and CT can also measure tophus volumes with excellent reproducibility CT can identify gouty erosions as hypodense lesions.The most exciting imaging advance in gout in recent years is the advent of DECT, which is able to detect MSU burden non-invasively. In addition to identifying crystals, advantages include:shorter scanning timesthe ability to scan multiple joints simultaneously have excellent reproducible visualization compared with US.

Magnetic Resonance Imaging (MRI)This is an excellent imaging modality to image synovium, cartilage, soft tissue and bone, as it lacks radiation and has excellent contrast and resolution. Limitations include high cost, availability, long scanning time, use of contrast, patient acceptability, and exclusion of those patients with aneurysm clips or pacemaker. MRI can demonstrate generic features of inflammatory arthritis, such as synovial thickening, effusion, bone erosions, and bone marrow edema (BME) in gout [Popp et al. 1996; Cimmino et al. 2011] (Figure 7 & Figure 8)

Nuclear MedicineFew systematic publications exist with regards to nuclear imaging in gout. While bone scan has high sensitivity in detecting osseous abnormality, the scintigraphic findings in gout are often non- specific (Figure 9)

ConclusionCR, US and DECT have the ability to assist in monitoring response to treat- ment. While others, like CT and MRI, have been demonstrated to aid our understanding of this dis- ease recently, and are likely to continue to be useful in proof-of-concept studies. Terima KasihWassalamualaikum Wr Wb